RT Journal Article
T1 Stromal SNAI2 is required for ERBB2 breast cancer progression
A1 Blanco Gómez, Adrián
A1 Hontecillas Prieto, Lourdes
A1 Corchado Cobos, Roberto
A1 García Sancha, Natalia
A1 Salvador Tormo, Nélida
A1 Castellanos Martín, Andrés
A1 Sáez Freire, María del Mar
A1 Mendiburu-Eliçabe Garganta, Marina
A1 Alonso López, Diego
A1 De Las Rivas Sanz, Javier
A1 Lorente Pérez, María Del Mar
A1 García Casas, Ana
A1 Del Carmen Martínez, Sofía
A1 Abad Hernández, María Del Mar
A1 Cruz Hernández, Juan Jesús
A1 Rodríguez Sánchez, César Augusto
A1 Claros Ampuero, Juncal
A1 García Cenador, Begoña
A1 García Criado, Javier
A1 Orimo, Akira
A1 Gridley, Thomas
A1 Pérez Losada, Jesús
A1 Castillo Lluva, Sonia
AB SNAI2 overexpression appears to be associated with poor prognosis in breast cancer, yet it remains unclear in which breast cancer subtypes this occurs. Here we show that excess SNAI2 is associated with a poor prognosis of luminal B HER2+/ERBB2+ breast cancers in which SNAI2 expression in the stroma but not the epithelium correlates with tumor proliferation. To determine how stromal SNAI2 might influence HER2+ tumor behavior, Snai2-deficient mice were crossed with a mouse line carrying the ErbB2/Neu protooncogene to generate HER2+/ERBB2+ breast cancer. Tumors generated in this model expressed SNAI2 in the stroma but not the epithelium, allowing for the role of stromal SNAI2 to be studied without interference from the epithelial compartment. The absence of SNAI2 in the stroma of HER2+/ERBB2+ tumors is associated with: (i) lower levels of cyclin D1 (CCND1) and reduced tumor epithelium proliferation; (ii) higher levels of AKT and a lower incidence of metastasis; (iii) lower levels of angiopoietin-2 (ANGPT2), and more necrosis. Together, these results indicate that the loss of SNAI2 in cancer-associated fibroblasts limits the production of some cytokines, which influences AKT/ERK tumor signaling and subsequent proliferative and metastatic capacity of ERBB2+ breast cancer cells. Accordingly, SNAI2 expression in the stroma enhanced the tumorigenicity of luminal B HER2+/ERBB2+ breast cancers. This work emphasizes the importance of stromal SNAI2 in breast cancer progression and patients' prognosis.
PB American Association of Cancer Research
SN 0008-5472
YR 2020
FD 2020
LK https://hdl.handle.net/20.500.14352/7993
UL https://hdl.handle.net/20.500.14352/7993
LA eng
NO Blanco-Gómez A, Hontecillas-Prieto L, Corchado-Cobos R, García-Sancha N, Salvador N, Castellanos-Martín A, et al. Stromal SNAI2 Is Required for ERBB2 Breast Cancer Progression. Cancer Research 2020;80:5216–30. https://doi.org/10.1158/0008-5472.CAN-20-0278.
NO Ministerio de Economía y Competitividad (España)
NO Instituto de Salud Carlos III 
NO Junta de Castilla y León
NO National Institutes of Health 
NO Sandra Ibarra Foundation for Solidarity against Cancer
NO “We can be heroes” Foundation
NO Federación Española de Enfermedades Raras
DS Docta Complutense
RD 18 dic 2025